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PubMed2000

Distribution of (76)Br-labeled antisense oligonucleotides of different length determined ex vivo in rats.

Oligonucleotides may hybridize with high selectivity to an RNA sequence and can be used for the monitoring of gene expression or for its inhibition in experimental or therapeutic purposes. As part of the development of positron emission tomography (PET) methods, different lengths (30, 20, 12 and 6 mer) of antisense phosphorothioate oligonucleotides complementary to rat chromogranin A were labeled with [(76)Br] using a prosthetic group. The (76)Br-oligonucleotides were injected into rat's tail vein (1-2 MBq/rat), and the radioactivity distribution was analyzed after 20 h using whole body autoradiography or by measurement of organ radioactivity concentration. The whole body autoradiography showed different distribution depending on the oligonucleotide length. The organs with highest uptake changed from kidney cortex (with 6 or 12 mer), kidney cortex and liver (with 20 mer), to liver and spleen (with 30 mer). With 20 or 30 mer sequences, uptake could be observed in the adrenals. Kidneys and livers from rats receiving 20 mer or 30 mer (76)Br-oligonucleotides were analyzed with respect to subcellular distribution and DNA/RNA/protein fraction. 30%-45% of the radioactivity was found in the nuclear fraction. More than 80% of the radioactivity was recovered in the high molecular weight fraction (as proteins or oligonucleotides longer than 10 mer) using size exclusion (NAP 5) gelfiltration or cetylpyridinium bromide (CPB) precipitation. This work indicates the potential to perform kinetic whole body studies of (76)Br-oligonucleotides using PET.

Animals↗
PubMed1995

Cadmium and zinc relationships in the liver and kidney of humans exposed to environmental cadmium.

Concentrations of cadmium and zinc were determined in the liver and in the kidney (cortex and medulla) of subjects from the general population of Barcelona (Spain) by atomic absorption spectrometry. Tissues were collected from necropsies of 50 selected subjects without any occupational exposure to heavy metals. Cadmium levels calculated on a fresh tissue basis were 14.6 +/- 5.9 micrograms/g (2.4-31) in the kidney cortex, 8.6 +/- 4.3 micrograms/g (1.5-16.7) in the kidney medulla and 0.98 +/- 0.50 micrograms/g (0.32-2.32) in the liver. Zinc concentrations ranged between 18-53 micrograms/g, (mean +/- S.D.: 38.0 +/- 10 micrograms/g) in the kidney cortex, 25.0 +/- 7.7 micrograms/g (12-42 micrograms/g) in the kidney medulla and 41.7 +/- 18.3 micrograms/g (20-84 micrograms/g) in the liver. The aim of the present work was to study the association of cadmium and zinc in the kidney and in the liver of a human population with cadmium accumulation from an environmental origin. The results obtained showed a significant correlation between cadmium and zinc concentration in the liver (r = 0.86, P < 0.001), but not in the kidney.

Adult↗
PubMed1990

The study of exposure to cadmium in the general population. I. Autopsy studies.

From 1982 to 1986 samples of materials (liver tissue, kidney cortex) were collected from 438 autopsies in Prague. The age of persons was over 50 years and residence time in the area was at least 10 years Concentrations of Cd and Zn were determined in the kidney cortex and the liver tissue using the AAS method. On the basis of the Questionnaire for Relatives, data on smoking habits, and occupational history of the investigated persons were obtained. The results of the study confirmed that the concentration of Cd in analyzed tissues did not exceed values reported in the literature for people of similar age living in Cd uncontaminated areas. In smokers significant increase of Cd in the kidney cortex was found in all age and sex groups. The body burden of Cd in smokers is significantly higher.

Adult↗
PubMed1986

Endogenous kallikrein inhibitor in rat kidney cortex-effect of glucocorticoid administration.

Kallikrein inhibiting proteins with two different molecular weight (6-8 X 10(4), 8-9 X 10(4) respectively) were observed in adrenalectomized rat kidney cortical soluble fraction. The larger one was observed in the kidneys of the adrenalectomized rats only when they had received chronic administration of excess amount of dexamethasone, and its kallikrein inhibitory activity was not lost with treatment with trypsin. This protein appears to be induced by chronic administration of glucocorticoid and might participate in the process of glucocorticoid regulating renal kallikrein kinin system.

Adrenalectomy↗
PubMed1982

Studies on the alpha-glucosidase specific for collagen disaccharide units: variations associated with capillary basement membrane thickening in kidney and brain of diabetic and aged rats.

The alpha-glucosidase specific for the hydroxylysine-linked disaccharide units of collagens (or 2-0-alpha-D-glucopyranosyl-5-0-beta-D-galactopyranosylhydroxy-L-lysine glucohydrolase) has been measured in kidney cortex and brain cortical tissue of streptozotocin diabetic rats after 19, 23 or 28 weeks of diabetes and of aged rats 22 months old. Increased specific activities of the enzyme have been found repeatedly in the dialyzed homogenates and the 7.2 X 10(6) g.min supernatants of kidney and brain at the various stages of diabetes when compared with age-matched controls; the specific activities returned to a normal level after insulin treatment. Similar increased specific activities were observed in kidney and brain of the aged normoglycemic rats when compared with young adult rats. In diabetic kidney cortex, beta-galactosidase and p-nitrophenyl-alpha-D-glucoside glucosidase specific activities were decreased in contrast to the increase of glucosyl-galactosyl-hydroxy-lysine glucohydrolase. In kidney cortex of the aged rats, beta-galactosidase activity was also decreased, but p-nitrophenyl-alpha-D-glucoside glucosidase was increased. In both diabetic and aged rats, thickening of the kidney glomerular basement membranes was confirmed; thickening of the brain cortical capillary basement membranes was also observed. Thus in the diabetic and aged animals, the increased glucosyl-galactosyl-hydroxylysine glucohydrolase specific activity was associated with basement membrane thickening in the kidney and the brain.

Aging↗
PubMed1975

Role of epithelial architecture and intracellular metabolism in proline uptake and transtubular reclamation in PRO/re mouse kidney.

The homozygous PRO/Re mouse has less than 1 percent of the very high proline oxidase activity that characterizes normal kidney cortex. In PRO/Re mouse the endogenous proline concentration is eight times normal in plasma and four times normal in kidney cortex cell, but 50 times normal in urine. The integrity of the membrane transport systems for proline uptake at the antiluminal surface of absorbing epithelium is retained in PRO/Re kidney, as determined by the slice method. Clearance studies in vivo under steady-state conditions indicate that the integrity of the luminal uptake system shared by glycine and proline, and serving proline absorption, is also intact. The exaggerated renal clearance of proline in PRO/Re mice (50 times normal) is explained when its raised intracellular concentration, caused by impaired proline oxidation, is considered. Backflux into urine flowing down the nephron will occur under these conditions, thus impairing net reclamation of proline in PRO/Re kidney. The findings reveal that membrane transport and intracellular metabolism of a substrate are, indeed, independent functions, but that metabolism of a substance can influence its transcellular transport.

Animals↗
PubMed1997

Proteolytic fragmentation reveals the oligomeric and domain structure of porcine aminopeptidase A.

Aminopeptidase A (glutamyl aminopeptidase; EC 3.4.11.7) has been cloned from porcine brain and kidney cortex cDNA libraries and the complete primary sequence of the enzyme deduced. This predicts a type II integral membrane protein of 942 amino acids with 14 potential N-linked glycosylation sites and a His-Glu-Xaa-Xaa-His zinc binding motif. Aminopeptidase A was purified from porcine kidney cortex by a combination of anion exchange and hydrophobic interaction chromatographies following its release from the membrane by trypsin. The purified protein migrated as three major polypeptides on SDS-polyacrylamide gel electrophoresis of M(r) 147,000, 107,000, and 45,000. N-Terminal sequencing revealed that both the Mr 147,000 and 107,000 polypeptides had the same N-terminal sequence resulting from cleavage of aminopeptidase A by trypsin at the Lys-42-Asp-43 bond just outside the membrane-spanning hydrophobic region. Immunoelectrophoretic blot analysis following electrophoresis under nonreducing conditions revealed that the trypsin-cleaved form of the enzyme no longer migrated as a disulfide-linked dimer, placing the interchain disulfide link N-terminal to Lys-42. N-Terminal sequencing of the M(r) 45,000 polypeptide in the purified preparation of aminopeptidase A revealed that it resulted from cleavage at the Asn-602-Gly-603 bond by an endogenous protease. This posttranslational proteolytic cleavage occurred in porcine kidney cortex microvillar membranes but not in porcine intestinal microvillar membranes. Incubation of purified porcine kidney aminopeptidase N (membrane alanyl aminopeptidase; EC 3.4.11.2) with trypsin resulted in a similar fragmentation pattern to that observed in aminopeptidase A, suggesting that these and other members of the type II membrane-spanning zinc aminopeptidase family may have two distinct domains: an N-terminal domain, containing the zinc binding site and residues identified as being involved in catalysis, and a C-terminal domain of unknown function, that are separated by a protease-susceptible region.

Amino Acid Sequence↗
PubMedDate not supplied

Relaxivity of Gd-EOB-DTPA in the normal and biliary obstructed guinea pig.

After injection of Gd-EOB-DTPA, T1 and T2 were determined on a clinical MR scanner (1.5 T) in the liver and kidneys of sacrificed but intact guinea pigs with normal and obstructed biliary systems and in bile, urine, and blood collected postmortem. Tissue [Gd] was determined by radioassay of 153Gd and relaxivities (R1 and R2; units of s(-1) x mmol(-1) x kg) of Gd-EOB-DTPA calculated. Compared with R1 in 2% agarose gel (4.49 +/- 0.03), in normal animals R1 was increased in liver (9.3 +/- 0.5), similar in kidney cortex (4.1 +/- 0.5), but reduced in kidney medulla (2.5 +/- 0.4) and papilla (2.7 +/- 0.4). Chronic biliary obstruction did not change R1 in liver (9.7 +/- 4.3) but reduced R1 further in kidney tissues (1.0-0.4). In normal animals, R2 values of all tissues (9.5-18.4) were greater than R2 in gel (5.72 +/- 0.12). Biliary obstruction possibly elevated R2 in liver (40.1 +/- 63.5), severely depressed R2 in kidney cortex (-4.2 +/- 6.2) and medulla (-2.3 +/- 5.4), and reduced R2 in papilla (5.4 +/- 4.6). Obstruction had little effect on R1 and R2 in bile and urine. Water content, macromolecular binding, microviscosity, compartmentalization, and susceptibility effects can readily account for the R1 and R2 observed in liver and kidney. Negative R2 could be a result of several factors, including reduced endogenous magnetic field gradients due to "susceptibility matching" as [Gd] increased, changes in tissue T2 with period of ligation, or a physiological effect of EOB-DTPA. These results show that disease can alter both R1 and R2 from their values in normal tissues.

Animals↗
PubMed2000

Characterization of receptors for osteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7) in rat kidneys.

BACKGROUND: Osteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7), a member of the transforming growth factor-beta superfamily, has been shown to prevent kidney damage from ischemia/reperfusion injury in rats. The molecular events involved in OP-1 action on kidney are not yet understood. METHODS: In this study, we evaluated the biodistribution of (125)I-labeled OP-1 in rat kidneys. Adult rats received a single intravenous injection of 250 microg (125)I-labeled OP-1 per kg body wt, a dose that was effective in protecting kidneys from ischemic injury. Tissue localization, in situ hybridization, and immunostaining with a specific receptor antibody were performed to identify OP-1 cellular targets. Also, isolated plasma membranes from kidney cortex and medulla regions were analyzed to identify and characterize receptor structural components that recognize OP-1. RESULTS: At 10 and 180 minutes following injection, the relative uptake of (125)I-labeled OP-1 was consistently higher in kidney cortex than in medulla region. Upon autoradiography, kidney tissue sections revealed that OP-1 bound to the convoluted tubule epithelium, glomeruli, and collecting ducts. Moreover, in situ hybridization and immunostaining methods have shown localization of mRNA transcripts and the protein for BMP receptor type II in the cortex and medulla in similar areas as (125)I-labeled OP-1. Bulk membranes (enriched with plasma membranes) isolated from the cortex and medulla regions of kidney each bound specifically to (125)I-OP-1, and the binding of (125)I-labeled OP-1 was inhibited by unlabeled OP-1 in a dose-dependent manner. However, platelet-derived growth factor, transforming growth factor-beta, insulin-like growth factor, fibroblast growth factors, and other members of BMP family such as BMP-2 and cartilage-derived morphogenetic protein-1/growth and differentiation factor-5 (CDMP-1/GDF-5) failed to inhibit the binding of (125)I-labeled OP-1 to receptors, suggesting a high degree of specificity with which OP-1 bound to kidney receptors. Scatchard analysis of quantitative binding data indicated that the OP-1 receptors of kidney contained a single class of high-affinity binding sites for OP-1 with an association constant (Ka) of 2.26 x 109 mol/L-1 and a binding capacity of 1.01 pmol of OP-1 per mg membrane protein. When analyzed by a ligand blot technique, plasma membranes isolated from kidney cortex and medulla each showed the presence of a prominent specific band with a relative molecular mass (Mr) of 100 kD. Further analysis by Western blotting indicated that an antibody raised against BMP type II receptor effectively recognized the 100 kD OP-1 binding component of kidney plasma membranes. CONCLUSIONS: We demonstrated, to our knowledge for the first time, the presence of membrane-bound, specific, high-affinity OP-1 receptors in rat kidney tissues, which are likely to mediate OP-1 actions in the kidney. The major OP-1-binding component of the kidney appears to be a long form of BMP type II receptor with a Mr of 100 kD. In vivo and in vitro evidence suggests that the cellular targets for OP-1 are convoluted tubule epithelium, glomeruli, and collecting ducts. OP-1 does not share receptor binding properties with other growth factors, including BMP-2 and CDMP-1, suggesting that its mode of action in kidney appears to be specific.

Animals↗
PubMed1988

Isocitrate dehydrogenase activity and its regulation by estradiol in tissues of rats of various ages.

The activity and hormonal regulation of NAD- and NADP-linked isocitrate dehydrogenase (EC.1.1.1.41 and EC.1.1.1.42, respectively) in the brain, liver and kidney cortex of female rats of various ages was investigated. The activity of NAD-ICDH of brain was greater than extramitochondrial (-c) or intramitochondrial (-m) NADP-ICDH. In contrast, liver c-NADP-ICDH was much higher than NAD- or m-NADP-ICDH, whereas in kidney cortex the activity of m-NADP-ICDH is dominant over both NAD- and c-NADP-ICDH in all the age group of rats studied. The activity of the NAD-ICDH of brain and all the enzymes of liver and kidney cortex increases until adulthood (33-weeks) and decreases thereafter in old rats (85-weeks). In brain c-NADP-ICDH was much higher in immature (6-weeks) rats and decreases with increasing age of the animal, whereas m-NADP-ICDH showed no significant change with the age of the rats. Bilateral ovariectomy decreases the level of all the three forms of enzyme in all the tissues of 6-, 13- and 33-week rats but failed to show any significant effect in 85-week old rats. Exogenous administration of estradiol induces all the three forms of enzyme in all the tissues of ovariectomized rats. The degree of response is tissue- and age-specific.

Aging↗
PubMed1990

Isolation and properties of bovine kidney brush border vacuolar H(+)-ATPase. A proton pump with enzymatic and structural differences from kidney microsomal H(+)-ATPase.

Vacuolar H(+)-ATPase was isolated from highly purified bovine kidney brush border, using a previously described immunoaffinity method. The affinity purified enzyme had reconstitutively active ATP-induced acidification that was inhibited by N-ethylmaleimide. The brush border H(+)-ATPase had a single pH optimum of 7.3, and a single Km for ATP of 360 microM. The enzyme showed no lipid activation; it had a substrate preference of ATP greater than ITP greater than UTP greater than GTP much greater than CTP, with an ATP:GTP selectivity of 1.69. The brush border H(+)-ATPase required no monovalent anion or cation for activity and was inhibited by the oxyanions NO3(-1) much greater than SO4(-2); sulfite stimulated activity at low concentrations and inhibited at higher concentrations. The inhibition produced by nitrate could not be attributed to dissociation of subunits from the enzyme. The divalent or trivalent cation preference was Mn+2 much greater than Mg+2 much greater than Co+2 greater than Al+3 greater than Ca+2 much greater than Ba+2,Sr+2; 1 mM Zn+2 inhibited the enzyme completely, but Cu+2 inhibited only 49% of activity at concentrations up to 5 mM. Sodium dodecyl sulfate-polyacrylamide gels of the brush border H(+)-ATPase showed subunits at Mr 70,000, a doublet at 56,000, 45,000, 42,000, 38,000, 33,000, 31,000, 15,000, 14,000, and 12,000. On two-dimensional gels, the pl value for the Mr 70,000 subunit was 6.3, for the Mr 56,000 was 6.4, and for the Mr 31,000 was 7.5-8.5, and microheterogeneity was observed in the Mr 56,000 and 31,000 subunits. A comparison of kidney cortex brush border H(+)-ATPase with kidney cortex microsomal H(+)-ATPase revealed differences in pH optimum, Km for ATP, lipid dependence, substrate preference, divalent ion preference, copper sensitivity, and in microheterogeneity of the Mr 56,000 and 31,000 subunits, providing evidence that different functional and structural classes of vacuolar H(+)-ATPase are segregated to specific membrane compartments.

Adenosine Triphosphate↗
PubMed1976

The purine nucleotide cycle. A pathway for ammonia production in the rat kidney.

Particle-free extracts prepared from kidney cortex of rat catalyze the formation of ammonia via the purine nucleotide cycle. The cycle generates ammonia and fumarate from aspartate, using catalytic amounts of inosine monophosphate, adenylosuccinate, and adenosine monophosphate. The specific activities of the enzymes of the cycle are 1.27+/-0.27 nmol/mg protein per min (SE) for adenoylosuccinate synthetase, 1.38+/-0.16 for adenylosuccinase, and 44.0+/-3.3 for AMP deaminase. Compared with controls, extracts prepared from kidneys of rats fed ammonium chloride for 2 days show a 60% increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity, and a greater and more rapid synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate. Extracts prepared from kidneys of rats fed a potassium-deficient diet show a twofold increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity. In such extracts the rate of synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate is also increased. These results show that the reactions of the purine nucleotide cycle are present and can operate in extracts of kidney cortex. The operational capacity of the cycle is accelerated by ammonium chloride feeding and potassium depletion, conditions known to increase renal ammonia excretion. Extracts of kidney cortex convert inosine monophosphate to uric acid. This is prevented by addition of allopurinol of 1-pyrophosphoryl ribose 5-phosphate to the reaction mixture.

AMP Deaminase↗
PubMed1983

Assessment of exposure to lead and cadmium through biological monitoring: results of a UNEP/WHO global study.

This paper describes a UNEP/WHO project on the assessment of human exposure to lead and cadmium through analysis of blood and kidneys. The following countries have participated: Belgium, India, Israel, Japan, Mexico, People's Republic of China, Peru, Sweden, United States, and Yugoslavia. No laboratory started the monitoring before achieving satisfactory results of quality control (QC) analysis (samples of cow blood spiked with lead and cadmium and freeze-dried horse kidney cortex for cadmium analysis) according to predetermined criteria based on a linear regression model. Two hundred teachers from one urban area in each country constituted the target group for lead and cadmium in blood and cases of "sudden, unexpected death" for cadmium in kidney cortex. QC samples were analyzed in parallel with the monitoring samples to assure validity of the obtained results. The quality assurance program also included preanalytical quality control. There was considerable variation in metal exposure between areas. Geometric means for lead in blood ranged from about 60 micrograms Pb/liter in Beijing and Tokyo to 225 in Mexico City. The values were below 100 micrograms Pb/liter also in Baltimore, Jerusalem, Lima, Stockholm, and Zagreb, and between 100 and 200 micrograms Pb/liter in Brussels and India. In general, males had higher blood levels than females and smokers higher than nonsmokers. With a few exceptions the values were lower than results reported in a recent study within the European Communities. Geometric means for cadmium in blood ranged from 0.5 microgram Cd/liter in Stockholm and Jerusalem to 1.2 in Brussels and Tokyo. Cadmium levels were considerably higher among smokers than among nonsmokers. Tokyo had the highest values for cadmium in kidney cortex with a geometric mean in the age group 40-60 years of 60-70 mg Cd/kg wet wt. Lowest values were found in Baltimore, Beijing, India, and Jerusalem, with means around 20-25 mg Cd/kg wet wt. There was a tendency toward higher values for smokers than for nonsmokers, but no differences related to sex. Data were not received from Mexico and Peru.

Animals↗
PubMed1989

Assay of tissue angiotensin converting enzyme.

The distinction between a circulating renin-angiotensin system and a tissue renin-angiotensin system led us to determine tissue angiotensin converting enzyme (ACE) activity. This study establishes the experimental conditions for a good reproducibility of the fluorimetric assay of ACE and describes the use of [3H]ramiprilat to characterize ACE. Angiotensin converting enzyme activity was determined in rat lung, heart, aorta, and kidney (cortex and medulla) and in rabbit kidney (cortex, medulla, tubules, and glomeruli). ACE activity and [3H]ramiprilat binding does not increase in a linear fashion with the protein content of tissue extracts. Linearity limits varied from 1.0 to 2.0 mg of protein/ml (fluorimetry) and from 0.4 to 1.0 mg of protein/ml [( 3H]ramiprilat binding). Comparing ACE activity, measured by fluorimetry, with the amount of [3H]ramiprilat bound shows that the two techniques yield similar results.

Animals↗
PubMed1984

Recovery of cortical phospholipidosis and necrosis after acute gentamicin loading in rats.

The recovery from gentamicin-induced phospholipidosis in the rat kidney cortex was characterized both morphologically and biochemically after a single 12-hr drug infusion. Total dosages administered were 10, 60, or 140 mg/kg, achieving constant serum concentrations of 3, 11, and 27 micrograms/ml, respectively. At the end of the 12-hr infusion, the cortical drug concentrations corresponding to the three dosages were 124, 450, and 993 micrograms/g of wet tissue. At the low dose (10 mg/kg), myeloid bodies were seen inside lysosomes of proximal tubular cells, along with a modest decrease of lysosomal sphingomyelinase activity. The cortical drug level declined steadily following first-order kinetics along with a disappearance of myeloid bodies and return of sphingomyelinase activity to control levels. At the high dose (140 mg/kg), we observed a sustained loss of sphingomyelinase activity (37% of controls), a subsequent increase of phospholipid concentration in the kidney cortex (up to 117% of controls 2 days after) and a prominent accumulation of myeloid bodies inside the lysosomes of proximal tubular cells (up to 4% of cell volume). Tubular regeneration and interstitial infiltration became detectable by histology and the increase of DNA synthesis as from day 1, along with an apparent reduction of the phospholipidosis at days 3 and 4. Drug cortical concentrations showed a sharp decline 2 days after infusion. An intermediate behavior was observed at 60 mg/kg. It is concluded that the proximal tubular cells behave in a fundamentally different way after gentamicin loading with low and high doses. At the low dose there is a regression of the drug-induced changes in the absence of any sign of necrosis-regeneration. Above a threshold in cortical drug concentration there is further development of the alterations leading to cell death-regeneration.

Animals↗
PubMed2004

Protective effects of Astragalus saponin I on early stage of diabetic nephropathy in rats.

Diabetic nephropathy (DN) has become the leading cause of end stage failure, but no renoprotective treatment has been very available for use in DN. Astragalus saponin I (AS I), a component extracted from Astragalus membranaceus BUNGE, was studied in experimental DN induced by administration of streptozotocin in male rats. The early DN rats were treated with 3 doses of AS I for 8 weeks to analyze its efficacy with different parameters. By comparison with vehicle-treated DN rats, the renal hypertrophy, the oxidative stress intensity, and the blood glucose level of DN rats were ameliorated by AS I. Also, the microalbuminuria level, advanced glycated end-products either in serum or in kidney cortex, and the aldose reductase activity were significantly reduced. Furthermore, the expression of transforming growth factor beta1 mRNA in kidney cortex by RT-PCR analysis was markedly declined. Both the relative grade of mesangium hyperplasia by microscopical observation and the thickness of glomerular base membrane by electron microscope measurement were decreased significantly. Therefore, the results suggest that AS I has therapeutic effects on several pharmacological targets in the progress of DN and is a potential drug for prevention of early stage DN.

Albuminuria↗
PubMed1996

Biochemical effects of Pembina Cardium crude oil exposure in cattle.

Crude oil pollution at drilling sites located within or in close proximity to agricultural pasture lands poses serious health risks to cattle raised on these lands. To investigate the clinical and systemic biochemical effects, cattle (8/group) were administered single oral doses of Pembina Cardium crude oil (PCCO) at 16.7, 33.4, and 67.4 g/kg, or water (control group) at 80 g/kg. Cattle exposed to PCCO showed dose-dependent clinical effects. At the lowest dosage, PCCO caused transient and minimal clinical effects; however, high dosages caused varied clinical signs which included tremors, nystagmus, vomiting, and pulmonary distress. On posttreatment day 7 or 30, four cattle from each treatment group were sacrificed and biochemical parameters were assayed in liver, lungs, and kidney cortex. In cattle monitored on posttreatment day 7, the PCCO-treated groups showed marked alterations from the control group in hepatic cytochrome P-450 (P-450), and in aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin-O-deethylase (ECOD) activities of these tissues. Administration of PCCO caused significant increases (> 100%) in hepatic P-450, but produced variable effects on AHH and ECOD activities in each tissue. The activity of AHH was increased in all tissues; however, the effect was highest in kidney cortex (> 5000%), followed by liver (> 500%) and lungs (> 250%). The activity of ECOD was altered in a differential manner. It was either increased markedly (>1300%) in kidney cortex or increased slightly (20-30%) in liver, but decreased (> 80%) in lungs. The activities of respiratory chain enzymes (succinate-cytochrome c reductase, NADH-cytochrome c reductase and cytochrome oxidase), or NADPH-cytochrome c reductase and glutathione transferase were not changed significantly in any tissues. The alterations in P-450, AHH, and ECOD observed on day 7 were markedly reversed in cattle examined on day 30 posttreatment, indicating a recovery from induced changes. Studies in vitro with hepatic microsomal preparations from day 7 posttreatment groups showed that increases in AHH and ECOD activity in PCCO-treated cattle were due to induction of new isoforms of P-450, as evidenced by (1) the appearance of a 448-nm spectral peak, and (2) differential inhibitory effects of metyrapone and 7,8-benzoflavone on AHH and ECOD activities.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2006

Use of tissue-fluid correlations to estimate gentamicin residues in kidney tissue of Holstein steers.

Gentamicin continues to be one of the most effective antibiotics for the treatment of gram-negative infections. Greater than 90% of the drug is rapidly eliminated from the body in <2 days, however, a small residue remains bound to the kidney cortex tissue for many months. In beef steers, the gentamicin residue is unacceptable and its presence is monitored by the FAST (Fast Antimicrobial Screen Test) applied to the kidney at the time of slaughter. The sensitivity of the FAST to gentamicin in the kidney cortex is reported to be 100 ng/g, therefore, this level of gentamicin defines the acceptable limit of gentamicin drug residue in the bovine kidney. In the present study, three doses of 4 mg/kg gentamicin was administered intramuscularly to eight steers. Gentamicin was allowed to deplete from the kidneys for a range of times from 7 to 10 months. At slaughter the level of gentamicin in the kidney cortex varied from 91 to 193 ng/g, but a total of 160 FAST tests performed on the kidneys were negative. Blood and urine samples were collected at varying times following the last dose of gentamicin. Kidney tissue samples were collected by laparoscopic surgery in the live steers as well as the final sample obtained at slaughter. Plasma levels of gentamicin declined rapidly to nondetectable within 3 days, while measurable urine persisted for 75 days before the concentration of gentamicin declined to levels too low to quantitate by the available liquid chromatography tandem mass spectrometry (LC/MS/MS) technique. An estimated correlation between an extrapolation of urine gentamicin concentration to the corresponding kidney tissue sample suggests a urine to kidney tissue relationship of 1:100. A test system sufficiently sensitive to a urine gentamicin concentration of 1 ng/mL will correlate with the estimated 100 ng/g gentamicin limit of the FAST applied to the fresh kidney of the recently slaughtered bovine.

Animals↗